Objective: To evaluate the functions of P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) in human colon adenocarcinoma (Caco-2), we carried out an in-vitro study and a small animal positron emission tomography (PET) study using [C]GF120918 (elacridar).
Methods: [C]GF120918 was synthesized by reacting the desmethyl precursor with [C]CH3I. An in-vitro study using [C]GF120918 was carried out in Caco-2 and Madin-Darby canine kidney cells in the presence or absence of a transporter inhibitor (cyclosporine A and unlabeled GF120918). The biodistribution of radioactivity after the injection of [C]GF120918 was determined in Caco-2-bearing mice using a small animal PET scanner.
Results: In Caco-2 cells expressing Pgp and BCRP, coincubation with unlabeled GF120918 caused an approximately two-fold increase in [C]GF120918 uptake compared with that of the control ([C]GF120918 only). In Caco-2-bearing mice, PET results indicated that [C]GF120918 uptake in the tumor was low, but was significantly increased by treatment with unlabeled GF120918. In metabolite analysis, the radioactive component in the tumor almost corresponded to intact [C]GF120918.
Conclusion: A PET study combining the administration of [C]GF120918 with unlabeled GF120918 may be a useful tool for evaluating the functions of Pgp and BCRP in tumors.